SEROTONIN CAUSES ACUTE GASTRIC-MUCOSAL INJURY IN RATS, PROBABLY VIA 5HT(1D) RECEPTORS

5-HT-induced acute gastric mucosal injury was assessed in rats by usin g 5HT(1), 5HT(2), 5HT(3), 5HT(4) or muscarinic receptor related drugs. Rats were treated with antagonists i.p. and 30 minutes later either v ehicle, 5-HT (20 mg/kg) or other agonists were administered s.c. The s tomachs were removed 4 hours after the last injection and mucosal inte grity was assessed by light microscopy using a histological ulcer inde x (HUI). The HUI was found to be significantly increased following 5-H T administration (1.57 +/- 0.3) when compared with controls (0.14 +/- 0.1). 5HT(1) agonist 5-carboxamidotryptamine (20 mg/kg) produced acute gastric erosion and increased the HUI (P < 0.05). The HUI in the anim als receiving 5-HT1D agonist sumatriptan (7 mg/kg) was found to be 1.6 2 +/- 0.24. 5HT(2) antagonist ketanserine (2.5-15 mg/kg), 5HT(3) antag onist ondansetron (1-5 mg/kg), 5HT(4) antagonist DAU 6285 (1-10 mg/kg) and atropine (1.5-30 mg/kg) exerted no effect whereas 5HT(1/2) antago nist metitepine (0.05-0.5 mg/kg) caused a dose dependent inhibition of the effect of 5-HT. The results from this study demonstrate that 5-HT causes acute gastric mucosal injury and this injury is probably due t o the activation of the 5-HT1D receptors.